Drug information of Desvenlafaxine
Mechanism of effect
Desvenlafaxine inhibits neurotransmitter reuptake in serotonin, norepinephrine, and dopamine transporters. Desvenlafaxine inhibits serotonin transporters with 10 times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity.
Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H1-histaminergic, or α1-adrenergic receptors in vitro. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity again the cardiac potassium channel, hERG, in vitro. Compared to other SNRIs, desvenlafaxine undergoes simple metabolism, has a low risk of drug-drug interactions and does not have to be extensively titrated to reach a therapeutic dose.
Peak plasma time: 7.5 hr
Ingestion of a high-fat meal (800-1000 calories) increased desvenlafaxine peak plasma concentration about 16% and had no effect on AUC
Protein bound: 30%
Vd: 3.4 L/kg
Primary: Conjugation (UDP-glucuronosyltransferase isoform mediated)
Minor: CYP3A4 oxidative metabolism (N-demethylation)
Enzymes inhibited: CYP2D6 (minimally)
Half-life: 11 hr (prolonged in renal or hepatic dysfunction)
Excretion, unchanged drug: Urine (45%)
Excretion, metabolite: 19% (glucuronide); <5% (oxidative metabolite [N,O-didesmethylvenlafaxine])
Major Depressive Disorder
50 mg PO once daily
Higher dosages, up to 400 mg/day, have been used but have not been proved more efficacious; increased side effects have been reported
Safety and efficacy not established
Drug contraindicationsConcomitant with MAOIs , excessive sensitivity to the drug or its component
Side effectsAnxiety , Insomnia , Diarrhea , Nosebleeds , Headache , Proteinuria , nausea , dry mouth , Seizures , Blurred vision , flushing , vertigo , asthenia , Tremor , urinary retention , extrapyramidal effects , tiredness , Rash , Syncope
InteractionsSibutramine , Tapentadol , safinamide , Almotriptan , Amphetamine , Amitriptyline , Ondansetron , Isoniazid , Imipramine , Buspirone , Paroxetine , Milnacipran , Dexfenfluramine , tedizolid , nalbuphine , Dolasetron , Palonosetron , Sufentanil , Alfentanil , Lorcaserin , L-Tryptophan , Fenfluramine , eletriptan , Mirtazapine , cocaine , Apixaban , Vilazodone , meperidine , Nefazodone , Dextroamphetamine , Pentazocine , Naratriptan , Frovatriptan , Remifentanil , Levorphanol , methylene blue , rasagiline , protriptyline , morphine , fentanyl , Cyclobenzaprine , Linezolid , lithium , Phenelzine , Amoxapine , Nortriptyline , Clomipramine , Zolmitriptan , escitalopram , ergotamine , Levodopa , Citalopram , Fluvoxamine , Fluoxetine , Granisetron , Maprotiline , Metoclopramide , Duloxetine , Doxepin , Dihydroergotamine , Rizatriptan , Sertraline , Selegiline , Procarbazine , Trazodone , Tramadol , Tranylcypromine , Trimipramine , Desipramine , Ramucirumab , Levomilnacipran , lasmiditan , vorapaxar , Netupitant
Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding
Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Use caution in patients with history of seizure disorders
Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants
May precipitate shift to mania or hypomania in patients with bipolar disorder; avoid monotherapy in patients with bipolar disorder; screen for bipolar disorder patients presenting with depressive symptoms
Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders
Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased
Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion
Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort
May impair congnitive abilities; use caution operating heavy machinery
Taper dose when possible and monitor for discontinuation symptoms; adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (eg, paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures
- Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort
- Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors
- Serotonin syndrome signs and symptoms may include mental status changes (eg, agitation, hallucinations, delirium, and coma), autonomic instability (eg, tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (eg, tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea)
- Monitor for the emergence of serotonin syndrome
- Discontinue treatment with desvenlafaxine and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment
- If concomitant use of desvenlafaxine with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms
Drug interactions overview
- Concomitant use of desvenlafaxine increases peak plasma concentration and AUC of a drug primarily metabolized by CYP2D6 which may increase the risk of toxicity of the CYP2D6 substrate drugs
- SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk
- False-positive urine immunoassay screening tests for phencyclidine (PCP) and amphetamine have been reported in patients taking desvenlafaxine
Black Box Warnings
Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies
Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years
In children and young adults, initiate only if benefits greatly outweigh risks
Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments
Patient’s family should communicate any abrupt behavioral changes to healthcare provider
Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy
Not approved for use in pediatric patients
Points of recommendation
Follow all directions on your prescription label and read all medication guides or instruction sheets. Use the medicine exactly as directed.
Take desvenlafaxine with water at the same time each day, with or without food.
Swallow the tablet whole and do not crush, chew, or break it.
Your blood pressure will need to be checked often.
It may take several weeks before your symptoms improve. Do not stop using desvenlafaxine without first talking to your doctor. You may have unpleasant side effects if you stop taking this medicine suddenly.
Some tablet forms of desvenlafaxine are made with a shell that is not absorbed or melted in the body. Part of the tablet shell may appear in your stool. This is a normal side effect and will not make the medicine less effective.
Store at room temperature away from moisture and heat.
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.